Cancer

Cancer is a term describing more than 100, possibly as many as 200, different diseases characterized by the common property of abnormal cell growth. Cancer is the second-leading cause of death in Canada and second only to accidents as a cause of death in children under 15 years of age. Approximately one of every 4 Canadians will die as a result of some form of cancer. Slightly more men than women develop cancer. Based on current incidence rates, about 40 percent of women and 45 percent of men will develop some type of cancer. Cancer is more prevalent among older Canadians; the majority of new cases and most deaths due to cancer occur among those over 70. However, with the development of improved screening tests and better treatment more than half of all people with cancer will survive the disease.

Some cancers (for instance, lung cancer) have become much more common since the 1940s; some (eg, breast cancer in women) have maintained a more or less steady incidence; and others (eg, cancers of the stomach and bladder and rectum) have become less prevalent. Lung cancer, currently the most preventable of all human cancers, is the leading cause of death among all cancer patients. Because of SMOKING, its incidence in young women now exceeds that of breast cancer. Lung cancer rates in Canadian men are decreasing, while the rates are only levelling off for Canadian women.

Colorectal cancer is the second-leading cause of death from cancer in Canada; breast cancer is the third-leading cause of cancer deaths and the most common cause in women. Prostate cancer is the most common form of cancer in men, although with improved screening and treatments fewer men are dying from this cancer. In order of mortality rates, according to the National Cancer Institute of Canada, other forms of cancers are pancreatic, urologic, uterine and oral, followed by leukemia and cancers of the ovary and skin. Skin cancer is actually the most common cancer by incidence, but its common forms are readily treatable and are not usually fatal.

Causes of Cancer

The body is made of billions of different types of cells that normally multiply at a rate just sufficient to compensate for cell losses. When they multiply uncontrollably a tumour (also called a neoplasm) results. There are 2 basic tumour types - benign and malignant. Benign (non-cancerous) tumours are those in which cells multiply but remain tightly together; adjacent tissues often develop a fibrous tissue (capsule) between themselves and the tumour. Benign tumours can be treated successfully by surgery. Malignant (cancerous) tumours can be locally invasive, ie, cells spread into adjacent tissues by sending out fingerlike probes. These potentially damaging tumours are often on the skin and often can be treated successfully with surgery or radiation.

Malignant tumours can also be metastatic. Such tumours are the most devastating, because they "seed" themselves via the blood and other body fluids. These seeds, or metastases, create a new tumour, called a secondary tumour. It was once believed that seeding occurred only when a tumour reached a certain size, and that if the tumour could be eliminated before it reached this size, the patient could be cured. Unfortunately, it is now known that metastatic tumours may seed long before they are detected.

The basis of malignant transformation remains unknown, but the recent discovery of oncogenes (cancer genes) is an important development in understanding cancer. In their inactive form these widespread genes are part of the normal genetic complement. Their structure has been carefully conserved during evolution, indicating that they have an important function in aiding the growth of normal cells. They may be activated and transformed by specific viruses or through minor mutations, which may be induced by radiation and some kinds of chemicals. They can also be activated by duplication, or by being attached to different chromosomes. Multiple (at least 2) genetic events appear to be needed for transformation (see GENETICS; VIRUS ). Oncogenes appear to contain the code for a number of small molecules called growth factors, which result in abnormal growth stimulation. Thus cancer can be thought of as a disorder of cellular growth and development.

Although the cause of human cancer cannot yet be explained fully at the molecular level, epidemiological studies have revealed the practical clinical significance of environmental hazards, social habits and genetic factors. Because of the prolonged period generally required for the development of cancer, it is difficult to analyse the exact roles of such factors, but 80% of all human cancers are thought to be related in some way to environmental factors and to be preventable. Two-thirds are preventable by not smoking and by dietary modifications. Hundreds of chemicals, including those used in foods as additives and preservatives, have been implicated, as have various drugs and radiation. About 40% of all cancers are thought to be related directly or indirectly to cigarette smoking. Viruses produce cancer in several animal species, including mammals, chickens, fish and frogs, but cause only about 5% of human cancers. For example, a number of specific types of the human papilloma virus (HPV) are involved in the development of cervical cancer.

Clinical Manifestations of Cancer

Particularly for the more common cancers, early detection and diagnosis are important for cure and prolonged survival. The Papanicolaou (Pap) smear has reduced the incidence and mortality of invasive cervical cancer. The National Cancer Institute of Canada (which, along with the Medical Research Council, funds cancer research in Canada), in co-operation with cancer agencies across Canada, is studying the effectiveness of screening programs for breast cancer using breast self-examination and mammography (over 90% of new breast cancers are discovered each year by patients).

The "Seven Steps to Health" (CANADIAN CANCER SOCIETY) are designed to encourage people to adopt healthy lifestyles and seek medical help for the early detection of cancers of the skin, breast, larynx, lung and genitourinary and gastrointestinal tracts. Possible cancer indicators include a change in bowel or bladder habits; a sore that does not heal; unusual bleeding or discharge; a thickening or a lump in the breast or elsewhere; indigestion or difficulty in swallowing; obvious change in a wart or mole; and nagging cough or hoarseness. Since cancer can affect any tissue and any bodily part, its clinical manifestations are very diverse and may often be silent for a long period before detection. The essential method of diagnosis is the examination of tissues or cells by a pathologist.

Principles of Therapy

In treating cancer it is assumed that all malignant cells should be destroyed, removed or neutralized. However, we do not know whether successful treatment must eradicate all malignant cells or merely reduce the cell number to a level where the patient's own defences can gain control. Five kinds of therapy exist today: surgery, radiotherapy, hormone therapy, chemotherapy and immunotherapy. Because cancer is not one but many different diseases, a combination of therapies is sometimes needed and will differ widely for each type of tumour.

For solid tumours, surgery and radiotherapy are used to treat the local disease. Metastatic disease requires a systemic therapy such as chemotherapy (use of anticancer drugs) which may be used initially or for secondary treatment. With malignancies involving the blood, chemotherapy may be the initial treatment. Chemotherapy often dramatically reduces the size of the tumour.

Approximately 50 drugs, which may be used singly or in various combinations, exist for the chemical management of cancer. Their mechanisms of action on the cancer cell are varied. Although their selective action is on tumour cells, normal tissues normal tissues that grow rapidly may also be damaged, leading to side effects such as reduced circulatory blood cells, loss of hair and bowel upset.

Tumours arising from the breast, prostate and uterine lining may respond to hormonal therapy. Certain hormones (eg, estrogens) may act by binding to specific receptors in the tumour cell. Breast and prostate cancers may be treated by removing sources of circulating hormones that could stimulate or support tumour growth. In some circumstances treatment may involve the administration of estrogens, androgens, progesterones, glucocorticoids or various pituitary peptides to suppress tumour growth.

New understanding of how the immune system defends the body has renewed interest in the use of immunotherapy as an adjuvant to surgery, chemotherapy and radiotherapy. For immunotherapy to be effective there must be a way to distinguish cancer cells from normal cells. Researchers have been exploring two methods of targeting and destroying cancer cells, both using monoclonal antibodies (proteins selected or engineered to recognize and bind to a specific type of cell). One approach would mark cancer cells for destruction by the immune system's T-cells. The second approach uses the antibody as a vehicle to deliver lethal doses of drugs directly to cancer cells.

There is great interest among researchers in the use of biologicals such as interferons, interleukins, vaccines and anti-antiogenesis factors (substances that block formation of blood vessels that nourish a tumour) for cancer therapy. These biologicals are substances produced by cells of the immune system, and have been made available to investigators as a result of recent advances in genetic engineering. They may be used alone or in combination with immune cells (LAK, or lymphokine activated killer, cells) from the patient which have been activated in the laboratory and then readministered. Surgical excision is still the current principal curative therapy, especially for those cancers that can be diagnosed early and removed completely. The surgeon is limited by the location and extent of the tumour rather than by its type.

Ionizing radiations of various types and energies are also used to destroy localized populations of cancer cells. As with surgery, results are best with relatively small tumours detected before they are locally or systemically widespread. The tolerance of adjacent normal tissues limits the amount of radiation that can be given. Although exact mechanisms are undefined, radiation appears to kill cells by interfering with their genetic apparatus through ionization of water molecules. Cobalt irradiation units and more recently computerized linear (electron) accelerators are being used, and research is being conducted on neutrons and atomic particles. Drugs are sometimes used to sensitize tumour tissues to radiation. Patients are generally informed of both the benefits and hazards of treatment.

New Research and Treatments

Canadian researchers are involved in a variety of projects to improve the understanding of the genetics involved in cancer, improving screening tools, and developing new techniques for cancer treatment.

Recent Canadian research on the genetic causes of medulloblastoma, a cancer of the cerebellum and the most common of childhood brain cancers, revealed 8 genes that, when mutated, are involved in cancer development. The research showed that when these genes are functioning normally their role is to make a protein that helps regulate the growth of the developing brain. When the genes mutate, brain cells can grow out of control and lead to cancer. The study provided a major breakthrough in the understanding of genetic causes of cancer. Brain tumours are a major cause of cancer death in children.

New Canadian STEM CELL RESEARCH has found a method of making blood from human stem cells. For the first time researchers have determined that one specific cell pathway is involved in prompting stem cells to become blood cells. The pathway apparently organizes stem cells so they can respond to cell specialization signals. This promising research could help develop a way to regenerate the blood system in cancer patients, such as those with leukemia, or those undergoing cancer treatments that indirectly destroy the blood and immune system.

Canadian researchers participating in a large international study on colorectal cancer helped identify 4 new colorectal cancer genes. This finding brings the total number of known genes connected with this common cancer to 10. Knowing these genetic markers could significantly improve screening, which remains one of the best methods of cancer prevention. The findings are also essential for identifying people at risk for colorectal cancer earlier, and to improve the understanding of cancer risk and its subsequent development. Colorectal cancer is the second-leading cause of cancer-related death in Canada.

A large international cancer research study recently suggested that a one-size-fits-all method of cancer treatment might not be the best approach. The study, led by a Canadian researcher, determined that a small percentage of colon cancer patients might not benefit from chemotherapy. This group has a specific genetic variant of colon cancer, which does not respond normally to chemotherapy. Treatment with chemotherapy for these patients could actually be harmful. A simple blood test can reveal the genetic type of colon cancer. The research illustrates the potential for more individually tailored cancer treatments in the future.

Cancer Services

During the past decade cancer services have been organized into regional comprehensive cancer centres in which are integrated the sophisticated technology needed for diagnosis and treatment, educational and consultative resources to surrounding communities, and clinical and basic research programs. In BC, Alberta, Saskatchewan, Manitoba, Ontario and the Maritimes cancer services are centrally organized and in many provinces registration of cancer patients is mandatory.

Cancer patients are managed largely as outpatients, often even in the terminal phase of illness. The early referral of cancer patients for multidisciplinary assessment by specialists is important; often the only chance for a cure is the first attempt at treatment. A wide variety of support services for patients and their families is also available across Canada through the Canadian Cancer Society and other community groups.

Psychosocial Aspects of Cancer

Much has been written about the psychosocial dimensions of terminal cancer, but cancer patients who survive also face severe psychological adjustments to accepting the diagnosis of a chronic and potentially fatal disease. Life with cancer still implies social unacceptability, including fear of painful suffering, disability, disfigurement, impaired bodily function, and loss of sexual attractiveness and self-esteem. It is commonly believed that once cancer has been diagnosed, a patient is helpless before the relentless onslaught of the disease. This misconception fuels the excessive sense of hopelessness and despair that characterizes the word "cancer." Current research is evolving a biology of host cell resistance to cancer, identifying mechanisms that are similar to those that operate to resist infections. Age, sex, immunity, hormones, nutrition, and psychological and probably other as yet undefined factors appear to influence resistance and help determine favourable or unfavourable outcomes, responses to treatment, and occasionally periods of long remission or even spontaneous regression.